The General Neural Simulation System (GENESIS) was first released for general use in 1988 as part of the first Methods in Computational Neuroscience Meeting at the Marine Biological Laboratory in Woods Hole, MA. Since its original release 19 years ago, GENESIS has provided one of the foundations for the growth of computational neuroscience both continuing to support education as well as research. With respect to summer courses, GENESIS continues to be part of the course in Woods Hole, as well as courses offered in the European Union, Mexico, India, Japan, and recently a new course in Brazil for Latin America. At last count GENESIS has also provided support for courses in at least 61 colleges and universities around the world where it has been used both as an instruction tool in realistic modeling of the nervous system, and as a simulation based tool for neurobiological education in general. The Book of GENESIS (Bower and Beeman, 1994, 1998), which was designed to support both computational and neurobiological instruction has sold more than 6,000 copies worldwide with more than double that number of copies having been distributed with the text now freely available on the Internet (Bower and Beeman, 2003). This substantial support for the use of GENESIS in instruction has also provided the base for extensive and growing use of this software system in biological research. Although certainly an underestimate, we are aware of 297 published GENESIS-dependent peer reviewed journal articles and book chapters not directly related to research in the P.I.'s laboratory. Further, more than a third of those reports (103) have been published during the period January 2004 to June 2007 (approximately the duration of the current NIH grant). As measured by the subjects of these publications, use of GENESIS has a growing emphasis on two types of simulations, those of large scale networks (using the parallel version of the platform), and those involving molecular biological modeling. GENESIS remains the only simulation system specifically designed from the outset to link multi-scale modeling efforts. With this grant, we seek continuing funding to support the expanding use of GENESIS, but also and importantly, to complete the implementation of a new version of the GENESIS platform. While maintaining backwards compatibility, GENESIS 3.0 is a complete rewrite and redesign of the system, replacing a 19-year-old structure. The rewrite will update and upgrade core GENESIS functionality while adding important new features, including model history control and tracking, a new web browser interface, and new features to support education as well as scholarly publication of models. Project Narrative Biological simulation technology is becoming an increasingly important part of both basic and translational research in medicine. The GENESIS system supported by this grant is one of the most used software systems supporting this type of research in the US, and will provide continuing support for the use and further development of this modeling platform. Newly proposed extensions include applications to medical education and scientific publishing as well as the continuing efforts to understand brain function and dysfunction.